Morphine is the natural alkaloid which gives opium its analgesic action. It has been known and used for centuries and still today is the standard against which new analgesics are measured. Extensive chemical modifications of morphine have produced analgesic substances of widely differing potency and addictive properties. Codeine, for example, the methyl ether of morphine, is a mild analgesic with only slight physical dependance liability. In contrast, the diacetyl derivative of morphine, heroin, is a powerful analgesic agonist with extremely high physical dependance liability. In addition to morphine and codeine, there are many other semisynthetic or totally synthetic derivatives and structures of opium type alkaloids, entailing several structurally distinct chemical classes of drugs displaying pharmacological properties related to those of morphine. Clinically useful drugs of this type include the morphinans, benzomorphans, methadones, phenylpiperidines, and propionanilides.
Recently several new drugs have been synthesized which have both analgesic agonist and antagonist properties with varying degrees of physical dependance liabilities. These new drugs in some cases can be viewed as morphine part-structures. For example, certain decahydroisoquinolines having a hydroxyphenyl group attached at the ring junction para to the isoquinoline nitrogen atom can be viewed as a morphine part-structure. Such compounds are the subject of Belgian Pat. No. 802,557.
An object of this invention is to provide certain N-substituted-5a-aryl-decahydrobenzazepines which can be viewed as being somewhat structurally related to certain morphine part-structures such as the aforementioned morphinans, benzomorphans, and isoquinoline derivatives. The compounds provided by this invention have not heretofore been described, as no method for their preparation has been available. Additionally, the compounds of this invention display an unpredictable variation in analgesic antagonist and agonist properties, but usually (invariably) with decreased physical dependance liability.